Pituitary Adenylate Cyclase Activating Peptide (PACAP) Participates in Adipogenesis by Activating ERK Signaling Pathway
Pituitary Adenylate Cyclase Activating Peptide (PACAP) Participates in Adipogenesis by Activating ERK Signaling Pathway
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DOI：
10.1371/journal.pone.0072607
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发表时间：
2013-09-09
期刊：
影响因子：
3.7
通讯作者：
Delporte, Christine
中科院分区：
文献类型：
--
作者：
Arsenijevic, Tatjana;Gregoire, Francoise;Delporte, Christine
腺苷酸环化酶激活肽（PACAP）属于胰泌素/胰高血糖素/血管活性肠肽（VIP）家族。它的作用可以由三种不同的受体亚型介导：PAC 1，其对PACAP具有排他性亲和力，以及VPAC 1和VPAC 2，其对PACAP和VIP具有相等的亲和力。我们发现，所有三种受体在3 T3- L1细胞分化成脂肪细胞的整个过程中表达。我们通过PACAP诱导后cAMP积累确定了这些受体的活性。PACAP与胰岛素、地塞米松联合诱导3 T3-L1细胞脂肪形成。PACAP在刺激后15 min内增加cAMP产生，并靶向MAPK（ERK 1/2）的表达和磷酸化，通过PACAP受体拮抗剂的不同组合部分或完全消除ERK 1/2磷酸化而加强。因此，我们推测ERK 1/2激活对CCAAT/增强子结合蛋白β（C/EBP β）的激活至关重要。
Pituitary adenylate cyclase activating peptide (PACAP) belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) family. Its action can be mediated by three different receptor subtypes: PAC1, which has exclusive affinity for PACAP, and VPAC1 and VPAC2 which have equal affinity for PACAP and VIP. We showed that all three receptors are expressed in 3T3- L1 cells throughout their differentiation into adipocytes. We established the activity of these receptors by cAMP accumulation upon induction by PACAP. Together with insulin and dexamethasone, PACAP induced adipogenesis in 3T3-L1 cell line. PACAP increased cAMP production within 15 min upon stimulation and targeted the expression and phosphorylation of MAPK (ERK1/2), strengthened by the ERK1/2 phosphorylation being partially or completely abolished by different combinations of PACAP receptors antagonists. We therefore speculate that ERK1/2 activation is crucial for the activation of CCAAT/enhancer-binding protein beta (C/EBP beta).